Unexpected reservoir of monocytes discovered in the spleen

July 30, 2009

It takes a spleen to mend a broken heart - that's the conclusion of a surprising new report from researchers at the Massachusetts General Hospital (MGH) Center for Systems Biology, directed by Ralph Weissleder, MD, PhD. In the July 31 issue of Science the team reports how, in following up an intriguing observation, they discovered an unexpected reservoir of the immune cells called monocytes in the spleen and went on to show that these cells are essential to recovery of cardiac tissue in an animal heart attack model.

"Monocytes are known to serve as a central defense system against injury, and we found that monocytes released from the spleen go directly to the injured heart and participate in wound healing," says Matthias Nahrendorf, MD, PhD, a co-lead author of the study.

Monocytes are generated in the bone marrow, released into the blood and are known to accumulate at injured or infected tissues, where they differentiate into macrophages or . In investigating processes involved in the healing of ischemic - the sort of injury produced in a heart attack - in mice, the research team was surprised to find more monocytes accumulating at the site of injury than would be found in the animals' entire . When they searched many types of tissue for the presence of cells with monocyte-specific molecules, they only found significant numbers of such cells in the spleen.

Monocytes in the spleen were identical in appearance, composition and function to monocytes in the blood. To investigate the splenic monocyte reservoir's potential involvement in cardiac healing, the researchers used several new technologies. A newly developed microscopic technique allowed them to determine how and where monocytes are stored in the spleen - previously known to store - and to study how monocytes are released in response to an experimentally-induced heart attack. A novel three-dimensional technique (fluorescence molecular tomography, developed at the MGH Center for Molecular Imaging Research) allowed study of monocyte-mediated immune functions at the site of heart muscle injury.

In mice whose spleens were removed and replaced with a donor organ, an induced heart attack led to rapid increase of spleen-derived donor monocytes in the bloodstream and massive accumulation of donor cells at the site of injury. In animals from whom spleens were removed but not replaced, heart attack produced no significant monocyte increase in the bloodstream or in the heart. "With all these approaches together, we found that the monocytes that travel to the heart after a heart attack come directly from the spleen and that, without the splenic monocytes, the heart tissue does not heal well," says Filip Swirski, PhD, co-lead author of the Science report.

The investigators also found that the hormone angiotensin II, known to be released in response to a heart attack, is actively involved in the release of monocytes from the . Identifying that pathway could lead to ways of manipulating the splenic monocyte reservoir to improve healing after a and potentially regulate other inflammatory situations. "We need to know whether this monocyte reservoir is important in other diseases - such as viral or bacterial infection, cancer or atherosclerosis - and understand how to precisely control storage and release of monocytes in a therapeutic setting, both of which we are currently investigating," says Mikael Pittet, PhD, senior author of the Science report.

Source: Massachusetts General Hospital (news : web)

Explore further: Role of a key enzyme in reducing heart disease identified

Related Stories

Role of a key enzyme in reducing heart disease identified

October 24, 2007

Virginia Commonwealth University researchers have identified the role of a key enzyme called CEH in reducing heart disease, paving the way for new target therapies to reduce plaques in the arteries and perhaps in the future, ...

Gene predicts heart attack response and cardiac damage

January 30, 2008

A protein has been found that influences the response of the heart to a lack of oxygen and blood flow, such as occurs during a heart attack, a team of Yale School of Medicine researchers report today in Nature.

Research identifies how inflammatory disease causes fatigue

February 17, 2009

New animal research in the February 18 issue of The Journal of Neuroscience may indicate how certain diseases make people feel so tired and listless. Although the brain is usually isolated from the immune system, the study ...

New origin found for a critical immune response

March 1, 2009

An immune system response that is critical to the first stages of fighting off viruses and harmful bacteria comes from an entirely different direction than most scientists had thought, according to a finding by researchers ...

Research defines dendritic cell lineage

March 19, 2009

(PhysOrg.com) -- Dendritic cells were discovered more than 30 years ago, but their pedigree has never been fully charted. They were known to be key immune system cells born in bone marrow, but their adolescence remained a ...

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

(PhysOrg.com) -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.